Haematological Malignancy - Acute Myeloid Leukaemia MedDRA version: 14.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Vidaza
Product Name: Azacitidine
Pharmaceutical Form: Lyophilisate for suspension for injection
INN or Proposed INN: azacitidine
CAS Number: 320-67-2
Current Sponsor code: azacitidine
Othe
Sponsors
The University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adults with AML in first relapse (except Acute Promyelocytic Leukaemia (APL) as defined by the World Health Organisation (WHO) Classification) who are deemed ineligible for intensive chemotherapy on the grounds of age or co-morbidities 2)Patients must have achieved a previous morphological CR as defined by Cheson criteria after treatment with conventional myelosuppressive chemotherapy e.g. anthracycline, ara-C, etoposide containing regimens 3)Patients are able to receive treatment as an out-patient 4)Adequate renal and hepatic function 5)Patients have given written informed consent 6)ECOG performance status =2 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
Exclusion criteria: 1)Patients with greater than class III of the New York Heart Association (NYHA) cardiac impairment 2)Blastic transformation of Chronic Myeloid Leukaemia (CML) 3)Any concurrent active malignancy 4)Prior allogeneic/autologous haematopoietic stem cell transplant (HSCT) 5)Pregnant or lactating women (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the start of treatment) 6) Adults of reproductive potential not willing to use appropriate medically approved contraception during the trial and for specified amount of time afterwards. 8)Patients who have received prior HDAC inhibitor-like treatment as anti-tumour therapy. (Patients who have received HDACi treatment for other indications e.g valproic acid for epilepsy may enrol after a 30-day washout period). 9)Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 30 days before the start of protocol treatment 10)Patients who have received prior treatment with demethylating agents such as 5-azacitidine or decitabine 11)Patients with contraindications to receiving azacitidine or vorinostat such as hypersenstivity or patients unable to receive subcutaneous injection 12)Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis. 13)Any co-morbidity that could limit compliance with the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To determine whether the combination therapy has an acceptable side effect profile, improves quality of life, improves CR rates, and does not significantly increase the supportive care requirements (blood product support/red cell and platelet transfusion requirements/days on antibiotics/days of hospitalisation).;Timepoint(s) of evaluation of this end point: 24 months;Main Objective: To evaluate the activity of azacitidine and vorinostat combined therapy, in terms of overall response (OR) (complete remission (CR), complete remission with incomplete blood count recovery (CRi) and partial remission (PR), as defined by Cheson criteria) and overall survival (OS) in patients with relapsed AML who are ineligible for intensive chemotherapy.;Primary end point(s): • Overall response rate (CR, CRi, PR), as defined by Cheson criteria and assessed within 6 cycles of treatment. • Overall survival, as defined as the time from date of randomisation to the date of death from any cause. Patients discontinuing study, lost to follow up or still alive at the end of the study will be censored at the date of last follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Toxicities will be measured and graded according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v4) from the date of randomisation until 28 days following treatment discontinuation. • Complete remission within 6 cycles of treatment as defined by Cheson criteria1 • Duration of response, defined as the time from achieving response to the time of relapse • Dose intensity defined as the total dose prescribed to each patient as a proportion of the protocol dose • Quality of Life will be measured using the EORTC QLQ-C30 and EuroQol EQ-5D questionnaire. • Resource use is defined in terms of days in hospital, blood product usage and days on anti-biotics from date of randomisation to 24 months follow up.;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
United Kingdom
Contacts
Public ContactRAVVA Trials Office (Haematology)
CRUK Clinical Trials Unit
Outcome results
None listed